It is known that polyanionic polysaccharides such as hyaluronic acid and alginic acid exhibit moderate viscosity, adhesiveness, moisture-retaining properties, and biocompatibility. These polyanionic polysaccharides and salts thereof are therefore widely used as a raw material for medical materials, food materials, cosmetic materials, and the like.
Among others, hyaluronic acid has excellent characteristic properties such as moisture-retaining properties, also has high safety and biocompatibility, and therefore is utilized for various applications such as foods, cosmetics, and pharmaceuticals. In a medical field for example, hyaluronic acid is utilized for a raw material or the like of lubricants for joints, adhesion inhibitors, etc. However, sodium hyaluronate being a raw material has a high water-solubility, and thus insolubilizing treatment of some sort has to be applied to sodium hyaluronate depending on the application.
Various studies have so far been conducted on the process for insolubilizing sodium hyaluronate in water through crosslinking reaction that makes use of a carboxy group. In Patent Literature 1 for example, a process for producing a water-insoluble derivative of a polyanionic polysaccharide such as hyaluronic acid and carboxymethylcellulose through crosslinking reaction using a carbodiimide is described.
Moreover, in Patent Literatures 2 and 3, a process for insolubilizing in water a polyanionic polysaccharide such as hyaluronic acid and a carboxyalkylcellulose by forming ionic bonds using a polyvalent cation is described. Further, in Patent Literature 4, a process for obtaining a water-insolubilized film by subjecting carboxymethylcellulose to ion exchange using a metal salt is described.
In Patent Literature 5, a process for insolubilizing sodium hyaluronate in water by cooling a sodium hyaluronate aqueous solution at −20° C. under an acidic condition to form intramolecular crosslinks is described. Moreover, in Patent Literature 6, acetylation of hyaluronic acid performed by reacting a hyaluronic acid in a powder form with acetic anhydride in the presence of concentrated sulfuric acid is described, and further, in Patent Literature 7, a process for producing hyaluronic acid gel using an acidic liquid containing an alcohol is described.